ROS1 is a receptor tyrosine kinase that is closely related to ALK, and, like ALK, it undergoes genomic rearrangement that creates fusion proteins in various cancers (Davies K D and Doebele R C (2013) Clin Cancer Res 19: 4040-4045). It is well established that these fusion proteins act as oncogenic drivers and that ROS1 inhibition is anti-proliferative in cells that express ROS1 fusions (Davies K D, Le A T, Theodoro M F, Skokan M C, Aisner D L, et al. (2012) Clin Cancer Res 18: 4570-4579). Thus, it appears that ROS1 targeted therapy will likely soon be the standard of care for this patient population. However, based on the experiences with other kinase inhibitors in various cancers, it is fully expected that acquired resistance to ROS1 inhibition will occur, and this will ultimately limit the treatment options for patients.